It has now become obvious that the pathophysiological defects leading to type 2 diabetes (T2D) is much more complex than thought
before. Insulin resistance is an early event in the course of T2D development. The transition from normoglycemy to prediabetes
is usually a gradual phenomenon that occurs over 5-10 years during which the disease remains undetected. Among the routinely
practiced T2D screening criteria, like FPG, IFG, IGT or HbA1c, still the issue of a preferable one is debated. Here I present more
precise non-invasive presymptomatic diagnosis and risk assessment strategies including noncoding RNAs signature in peripheral
blood.
Life style changes with addition of metformin, sulphonylureas, glinides, α-glucosidase inhibitors, thiazolidinediones and/or exogenous
insulin are recommended as the present treatment options. These treatments offer improvement in glycemic control, but in many
instances produce significant adverse side effects. Various novel incretin-based therapies like prolonging GLP-1 receptor agonists
action, orally GLP-1 receptor agonists, GLP-1 secretion by activating GLP-1-producing intestinal L-cells, synthetic engineered
peptides as co-agonists stimulating more than one receptor, etc. are discussed here.
I also present our experiences regarding development of successful gene therapy using intestinal K-cells which are specialized for GIP
production. Engineering these cells to produce insulin in response to the ingested carbohydrates successfully achieved. Oral gene
delivery to these cells using nanoparticles with appropriate protective coats as well as plant exosomal gene delivery to the stem cell
precursors of K-cells located at the base of intestinal crypts resulted in long lasting insulin expression by gut K-cells and pronounced
treatment of T2D.